To a solution of N-{3-[(2-amino-7-cyano-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (150 mg, 0.33 mmol) produced in Example 1 (iv) in N,N-dimethylacetamide (3 mL) was added chloroacetyl chloride (58 μL, 0.73 mmol), and the mixture was stirred at room temperature for 2 hr. 5% Aqueous sodium hydrogen carbonate solution (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (10 mL). The extract was washed with saturated brine (10 ml), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, the filtrate was concentrated under reduced pressure, the obtained residue was dissolved in tetrahydrofuran (3 mL). Triethylamine (136 μL, 0.99 mmol) and 1-methylpiperazine (110 μL, 0.99 mmol) were added to the mixture, and the mixture was stirred at 80° C. for 8 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), washed successively with water (10 mL) and saturated brine (10 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100→15/85). The obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/diisopropyl ether to give the title compound (126 mg, 64%) as a white powder.
